Very early remission and increased apoptosis with the use of Pentoxifylline in children with acute lymphoblastic leukemia
IntroductionDespite the improvement in survival in acute lymphoblastic leukemia (ALL), there are still cases with evasion of chemotherapy-induced apoptosis. The IKK/NF-κB signaling pathway contributes to antiapoptotic gene expression. Pentoxifylline (PTX) inhibits IkB phosphorylation, blocking NF-κB...
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Frontiers Media S.A.
2024-10-01
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| author | Violeta Salceda-Rivera Violeta Salceda-Rivera Violeta Salceda-Rivera Pablo C. Ortiz-Lazareno Pablo C. Ortiz-Lazareno Georgina Hernández-Flores Jorge R. Vazquez-Urrutia Jorge R. Vazquez-Urrutia Jesus Meza-Arroyo Monzerrat Pardo-Zepeda Monzerrat Pardo-Zepeda Hugo Romo-Rubio Cesar Barba-Barba Fernando Sánchez-Zubieta Fernando Sánchez-Zubieta Carlos Alfredo Barrón-Gallardo Oscar Gonzalez-Ramella Oscar Gonzalez-Ramella Oscar Gonzalez-Ramella Alejandro Bravo-Cuellar Alejandro Bravo-Cuellar Alejandro Bravo-Cuellar |
| author_facet | Violeta Salceda-Rivera Violeta Salceda-Rivera Violeta Salceda-Rivera Pablo C. Ortiz-Lazareno Pablo C. Ortiz-Lazareno Georgina Hernández-Flores Jorge R. Vazquez-Urrutia Jorge R. Vazquez-Urrutia Jesus Meza-Arroyo Monzerrat Pardo-Zepeda Monzerrat Pardo-Zepeda Hugo Romo-Rubio Cesar Barba-Barba Fernando Sánchez-Zubieta Fernando Sánchez-Zubieta Carlos Alfredo Barrón-Gallardo Oscar Gonzalez-Ramella Oscar Gonzalez-Ramella Oscar Gonzalez-Ramella Alejandro Bravo-Cuellar Alejandro Bravo-Cuellar Alejandro Bravo-Cuellar |
| author_sort | Violeta Salceda-Rivera |
| collection | DOAJ |
| description | IntroductionDespite the improvement in survival in acute lymphoblastic leukemia (ALL), there are still cases with evasion of chemotherapy-induced apoptosis. The IKK/NF-κB signaling pathway contributes to antiapoptotic gene expression. Pentoxifylline (PTX) inhibits IkB phosphorylation, blocking NF-κB and antiapoptotic activity. MethodsWe conducted a randomized, double-blind clinical trial on pediatric ALL patients undergoing induction therapy, assigning them to PTX or placebo group. Bone marrow aspirates were obtained on days 1, 8, 15, and 22. Apoptosis was assessed using Annexin-V/propidium iodide. ResultsResults indicated that the PTX group exhibited higher apoptosis on day-8 (41.3% vs. 19.4%, p =0.029) and day-15 (35.0% vs. 14.2%, p <0.01). On day-8, the PTX group displayed an MRD of 0.25% vs. 18.2% (p <0.01) in placebo group; on day-15, the PTX group demonstrated an MRD of 0.09% vs. 1.4% (p =0.02). Patients achieving an MRD <0.01% on day-8 demonstrated a 3-year Overall Survival (OS) of 81.6% vs. 58.3% (p =0.03); on day-15, patients with MRD <0.01% had a 3-year OS of 77.9% vs. 54.5% (p =0.03). The PTX group achieved an MRD of <0.01% earlier on days-8 and 15, along with a higher apoptosis rate, indicating a more favorable therapeutic response. In the entire cohort, patients achieving MRD <0.01% on day-8 or 15 displayed superior OS. ConclusionOur study demonstrates that PTX enhances apoptosis and reduces MRD in pediatric acute lymphoblastic leukemia patients.Clinical trial registrationhttps://clinicaltrials.gov/, identifier NCT02451774. |
| format | Article |
| id | doaj-art-eaa1036d7e2446648ebaaec56c85f97c |
| institution | OA Journals |
| issn | 2234-943X |
| language | English |
| publishDate | 2024-10-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Oncology |
| spelling | doaj-art-eaa1036d7e2446648ebaaec56c85f97c2025-08-20T02:01:45ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2024-10-011410.3389/fonc.2024.14012621401262Very early remission and increased apoptosis with the use of Pentoxifylline in children with acute lymphoblastic leukemiaVioleta Salceda-Rivera0Violeta Salceda-Rivera1Violeta Salceda-Rivera2Pablo C. Ortiz-Lazareno3Pablo C. Ortiz-Lazareno4Georgina Hernández-Flores5Jorge R. Vazquez-Urrutia6Jorge R. Vazquez-Urrutia7Jesus Meza-Arroyo8Monzerrat Pardo-Zepeda9Monzerrat Pardo-Zepeda10Hugo Romo-Rubio11Cesar Barba-Barba12Fernando Sánchez-Zubieta13Fernando Sánchez-Zubieta14Carlos Alfredo Barrón-Gallardo15Oscar Gonzalez-Ramella16Oscar Gonzalez-Ramella17Oscar Gonzalez-Ramella18Alejandro Bravo-Cuellar19Alejandro Bravo-Cuellar20Alejandro Bravo-Cuellar21Immunology Division, Western Biomedical Research Center, Mexican Social Security Institute, Guadalajara, JAL, MexicoDoctoral Program in Biomedical Sciences, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, JAL, MexicoDepartment of Pediatric Hemato-Oncology, Hospital Civil de Guadalajara “Dr. Juan I. Menchaca”, Guadalajara, JAL, MexicoImmunology Division, Western Biomedical Research Center, Mexican Social Security Institute, Guadalajara, JAL, MexicoDoctoral Program in Biomedical Sciences, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, JAL, MexicoImmunology Division, Western Biomedical Research Center, Mexican Social Security Institute, Guadalajara, JAL, MexicoImmunology Division, Western Biomedical Research Center, Mexican Social Security Institute, Guadalajara, JAL, MexicoCentro Universitario de Ciencias de la Salud, School of Medicine, Universidad de Guadalajara, Guadalajara, JAL, MexicoDoctoral Program in Biomedical Sciences, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, JAL, MexicoDoctoral Program in Biomedical Sciences, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, JAL, MexicoDepartment of Pediatric Hemato-Oncology, Hospital Civil de Guadalajara “Dr. Juan I. Menchaca”, Guadalajara, JAL, MexicoDepartment of Pediatric Hemato-Oncology, Hospital Civil de Guadalajara “Dr. Juan I. Menchaca”, Guadalajara, JAL, MexicoDepartment of Pediatric Hemato-Oncology, Hospital Civil de Guadalajara “Dr. Juan I. Menchaca”, Guadalajara, JAL, MexicoDepartment of Pediatric Hemato-Oncology, Hospital Civil de Guadalajara “Dr. Juan I. Menchaca”, Guadalajara, JAL, MexicoDepartamento de Clinicas de Reproduccion Humana, Crecimiento y Desarrollo Infantil, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, JAL, MexicoDepartamento Académico de Disciplinas Especializantes de Ciencias de la Salud, Universidad Autonoma de Guadalajara, Zapopan, JAL, MexicoDoctoral Program in Biomedical Sciences, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, JAL, MexicoDepartment of Pediatric Hemato-Oncology, Hospital Civil de Guadalajara “Dr. Juan I. Menchaca”, Guadalajara, JAL, MexicoCentro Universitario de Ciencias de la Salud, School of Medicine, Universidad de Guadalajara, Guadalajara, JAL, MexicoImmunology Division, Western Biomedical Research Center, Mexican Social Security Institute, Guadalajara, JAL, MexicoDoctoral Program in Biomedical Sciences, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, JAL, MexicoCentro Universitario de los Altos, Universidad de Guadalajara, Tepatitlán de Morelos, JAL, MexicoIntroductionDespite the improvement in survival in acute lymphoblastic leukemia (ALL), there are still cases with evasion of chemotherapy-induced apoptosis. The IKK/NF-κB signaling pathway contributes to antiapoptotic gene expression. Pentoxifylline (PTX) inhibits IkB phosphorylation, blocking NF-κB and antiapoptotic activity. MethodsWe conducted a randomized, double-blind clinical trial on pediatric ALL patients undergoing induction therapy, assigning them to PTX or placebo group. Bone marrow aspirates were obtained on days 1, 8, 15, and 22. Apoptosis was assessed using Annexin-V/propidium iodide. ResultsResults indicated that the PTX group exhibited higher apoptosis on day-8 (41.3% vs. 19.4%, p =0.029) and day-15 (35.0% vs. 14.2%, p <0.01). On day-8, the PTX group displayed an MRD of 0.25% vs. 18.2% (p <0.01) in placebo group; on day-15, the PTX group demonstrated an MRD of 0.09% vs. 1.4% (p =0.02). Patients achieving an MRD <0.01% on day-8 demonstrated a 3-year Overall Survival (OS) of 81.6% vs. 58.3% (p =0.03); on day-15, patients with MRD <0.01% had a 3-year OS of 77.9% vs. 54.5% (p =0.03). The PTX group achieved an MRD of <0.01% earlier on days-8 and 15, along with a higher apoptosis rate, indicating a more favorable therapeutic response. In the entire cohort, patients achieving MRD <0.01% on day-8 or 15 displayed superior OS. ConclusionOur study demonstrates that PTX enhances apoptosis and reduces MRD in pediatric acute lymphoblastic leukemia patients.Clinical trial registrationhttps://clinicaltrials.gov/, identifier NCT02451774.https://www.frontiersin.org/articles/10.3389/fonc.2024.1401262/fullMRDALLclinical trialsapoptosisPentoxifyllineearly remission |
| spellingShingle | Violeta Salceda-Rivera Violeta Salceda-Rivera Violeta Salceda-Rivera Pablo C. Ortiz-Lazareno Pablo C. Ortiz-Lazareno Georgina Hernández-Flores Jorge R. Vazquez-Urrutia Jorge R. Vazquez-Urrutia Jesus Meza-Arroyo Monzerrat Pardo-Zepeda Monzerrat Pardo-Zepeda Hugo Romo-Rubio Cesar Barba-Barba Fernando Sánchez-Zubieta Fernando Sánchez-Zubieta Carlos Alfredo Barrón-Gallardo Oscar Gonzalez-Ramella Oscar Gonzalez-Ramella Oscar Gonzalez-Ramella Alejandro Bravo-Cuellar Alejandro Bravo-Cuellar Alejandro Bravo-Cuellar Very early remission and increased apoptosis with the use of Pentoxifylline in children with acute lymphoblastic leukemia Frontiers in Oncology MRD ALL clinical trials apoptosis Pentoxifylline early remission |
| title | Very early remission and increased apoptosis with the use of Pentoxifylline in children with acute lymphoblastic leukemia |
| title_full | Very early remission and increased apoptosis with the use of Pentoxifylline in children with acute lymphoblastic leukemia |
| title_fullStr | Very early remission and increased apoptosis with the use of Pentoxifylline in children with acute lymphoblastic leukemia |
| title_full_unstemmed | Very early remission and increased apoptosis with the use of Pentoxifylline in children with acute lymphoblastic leukemia |
| title_short | Very early remission and increased apoptosis with the use of Pentoxifylline in children with acute lymphoblastic leukemia |
| title_sort | very early remission and increased apoptosis with the use of pentoxifylline in children with acute lymphoblastic leukemia |
| topic | MRD ALL clinical trials apoptosis Pentoxifylline early remission |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2024.1401262/full |
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